It is proposed to study the role of cyclic AMP and protein phosphorylation in normal and abnormal brain function and in the mechanism of action of antipsychotic drugs. The specific program to be undertaken involves studies in five areas: (1) investigating the possibility that psychoactive drugs (antischizophrenic drugs, hallucinogenic drugs, and antidepressants drugs) affect the state of phosphorylation of Protein I in vivo; (2) finding other substrates for cyclic AMP-dependent protein kinases and calcium-dependent protein kinases in synaptosomes and synaptic membrane fractions; (3) evaluating the possible involvement of Protein I and of other synaptic phosphoproteins in neurotransmitter release and neurotransmitter action; (4) evaluating the role of phosphoprotein regulation of microtubule function; and (5) developing a cytochemical method for localizing cyclic AMP-dependent protein kinases and cyclic GMP-dependent protein kinases in nervous tissue.